Abstract：
:Xenobiotic metabolism, a ubiquitous natural response to foreign compounds, elicits initiating signals for many pathophysiological events. Currently, most widely used techniques for identifying xenobiotic metabolites and metabolic pathways are empirical and largely based on in vitro incubation assays and in vivo radiotracing experiments. Recent work in our lab has shown that LC-MS-based metabolomic techniques are useful tools for xenobiotic metabolism research since multivariate data analysis in metabolomics can significantly rationalize the processes of xenobiotic metabolite identification and metabolic pathway analysis. In this review, the technological elements of LC-MS-based metabolomics for constructing high-quality datasets and conducting comprehensive data analysis are examined. Four novel approaches of using LC-MS-based metabolomic techniques in xenobiotic metabolism research are proposed and illustrated by case studies and proof-of-concept experiments, and the perspective on their application is further discussed.
journal_name
Drug Metab Revjournal_title
Drug metabolism reviewsauthors
Chen C,Gonzalez FJ,Idle JRdoi
10.1080/03602530701497804subject
Has Abstractpub_date
2007-01-01 00:00:00pages
581-97issue
2-3eissn
0360-2532issn
1097-9883pii
781831943journal_volume
39pub_type
杂志文章,评审abstract：:Cytochrome P450 2D6 (CYP2D6) is a polymorphic enzyme responsible for metabolizing approximately 25% of all drugs. CYP2D6 is highly expressed in the brain and plays a role as the major CYP in the metabolism of numerous brain-penetrant drugs, including antipsychotics and antidepressants. CYP2D6 activity and inhibition h...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2015.1047026
更新日期：2015-08-01 00:00:00
abstract：:Voriconazole, a second-generation triazole frequently used for the prophylaxis and treatment of invasive fungal infections, undergoes complex metabolism mainly involving various (polymorphic) cytochrome P450 enzymes in humans. Although high inter- and intraindividual variability in voriconazole pharmacokinetics have b...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2019.1632888
更新日期：2019-08-01 00:00:00
abstract：:Hyperbilirubinemia may accompany harmful effects such as jaundice, brain dysfunction, and pharmacokinetic alterations of drugs. Clinical drugs are the important causes of hyperbilirubinemia, especially for patients with certain pathologic conditions or with genetic variations. This article reviews hyperbilirubinemic p...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530802341133
更新日期：2008-01-01 00:00:00
abstract：:This article reviews the regulatory, social, policy, and other issues that will shape the development of pharmacogenomics applications. We identify and analyze 19 key public policy issues, ranging from the economic incentives for linked diagnostic-drug development, to the regulation of tests and drugs, and to privacy ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530801952500
更新日期：2008-01-01 00:00:00
abstract：:Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the "magic mushrooms" and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT)2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic releva...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2016.1278228
更新日期：2017-02-01 00:00:00
abstract：:Chemicals that cause toxicity though a direct mechanism, such as acetaminophen, covalently bind to a select group of proteins prior to the development of toxicity, and these proteins may be important in the initiation of the events that lead to the hepatotoxicity. Disruption of the cell is measured by release of intra...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602539709037572
更新日期：1997-02-01 00:00:00
abstract：:Cytochrome P450-based cancer gene therapy is a novel prodrug activation strategy for cancer treatment that has substantial potential for improving the safety and efficacy of cancer chemotherapeutics. The primary goal of this strategy is to selectively increase tumor cell exposure to cytotoxic drug metabolites generate...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-100101933
更新日期：1999-05-01 00:00:00
abstract：:The present paper has discussed available test systems for determination of the response of G-6-PD-deficient human erythrocytes to environmental agents. The limitations and advantages of each model have been examined, and the results of research using each model have been presented. The future development of suitable ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602538608998292
更新日期：1986-01-01 00:00:00
abstract：:Hormone-dependent breast cancers that overexpress the ligand-binding nuclear transcription factor, estrogen receptor (ER), represent the most common form of breast epithelial malignancy. Exposure of breast epithelial cells to a redox-cycling and arylating quinone induces mitogen-activated protein kinase phosphorylatio...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530600959391
更新日期：2006-01-01 00:00:00
abstract：:Flavin-containing monooxygenases (FMOs) are important oxidative drug metabolizing enzymes. FMO3 is the primary human adult liver FMO enzyme, but is developmentally regulated. FMO3 promoter characterization using in vitro DNA binding assays with HepG2 cell and fetal and adult liver nuclear protein, as well as FMO3/repo...
journal_title：Drug metabolism reviews
pub_type： 杂志文章
doi：10.1080/03602530701498612
更新日期：2007-01-01 00:00:00
abstract：:For patients undergoing cardiopulmonary bypass (CPB) during cardiac surgery, there are well-documented changes in the pharmacokinetics (PK) of commonly administered drugs. Although multiple factors potentially underpin these changes, there has been scant research attention on the impact of CPB to alter the activities ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2017.1417423
更新日期：2018-05-01 00:00:00
abstract：:Dehydroepiandrosterone has been thought to have physiological functions other than as an androgen precursor. The previous studies performed have demonstrated a number of biological effects in rodents, such as amelioration of disease in diabetic, chemical carcinogenesis, and obesity models. To date, activation of the p...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530600569877
更新日期：2006-01-01 00:00:00
abstract：:Gold Nanostars (GNS) have attracted tremendous attention toward themselves owing to their multi-branched structure and unique properties. These state of the art metallic nanoparticles possess intrinsic features like remarkable optical properties and exceptional physiochemical activities. These star-shaped gold nanopar...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2020.1734021
更新日期：2020-05-01 00:00:00
abstract：:The cannabinoid receptor 1 (CB1) is a G protein-coupled receptor (GPCR) that is located primarily in the central nervous system. CB1 is a therapeutic target which may impact pathways to mediate pain, neurodegenerative disorders, hunger, and drug-seeking behavior. Despite these benefits, development of orthosteric ther...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2018.1428342
更新日期：2018-02-01 00:00:00
abstract：:Glutathione S-transferase P1-1 (GSTP) is one member of the family of GSTs and is ubiquitously expressed in human tissues. The literature is replete with reports of high levels of GSTP linked either with cancer incidence or drug resistance, and yet no entirely cogent explanation for these correlations exists. The catal...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2011.552912
更新日期：2011-05-01 00:00:00
abstract：:Glycyrrhizic acid is widely applied as a sweetener in food products and chewing tobacco. In addition, it is of clinical interest for possible treatment of chronic hepatitis C. In some highly exposed subjects, side effects such as hypertension and symptoms associated with electrolyte disturbances have been reported. To...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-100104400
更新日期：2001-05-01 00:00:00
abstract：:The Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB: http://www.pharmgkb.org) is devoted to disseminating primary data and knowledge in pharmacogenetics and pharmacogenomics. We are annotating the genes that are most important for drug response and present this information in the form of Very Important ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章
doi：10.1080/03602530802413338
更新日期：2008-01-01 00:00:00
abstract：:The high rate of attrition during drug development and its associated high research and development (R&D) cost have put pressure on pharmaceutical companies to ensure that candidate drugs going to clinical testing have the appropriate quality such that the biological hypothesis could be evaluated. To help achieve this...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2012.691099
更新日期：2012-08-01 00:00:00
abstract：:Pregnane X receptor (PXR) and constitutive active/androstane receptor (CAR), members of the nuclear receptor superfamily, are two major xeno-sensing transcription factors. They can be activated by a broad range of lipophilic xenobiotics including therapeutics drugs. In addition to xenobiotics, endogenous compounds suc...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2013.835630
更新日期：2013-11-01 00:00:00
abstract：:Acetaminophen (APAP, paracetamol, N-acetyl-p-aminophenol) is a widely used analgesic that is safe at therapeutic doses but is a major cause of acute liver failure (ALF) following overdose. APAP-induced hepatotoxicity is related to the formation of an electrophilic reactive metabolite, N-acetyl-p-benzoquinone imine (NA...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2014.982865
更新日期：2015-02-01 00:00:00
abstract：:Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is associated with decreased quality of life, and increased mortality and morbidity from stroke and thromboembolism. The underlying mechanisms involved in the development of AF have yet to be fully elucidated. However, once initiated, AF t...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2015.1077858
更新日期：2015-08-01 00:00:00
abstract：:Like any other drugs, antiallergic medications can be associated with large inter- and intraindividual variability in their disposition. The best-documented examples belong to the H1 antihistamines. Variable drugs are more likely to show unpredictable therapeutic response with both increased risks of side effects and ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/10837450902891485
更新日期：2009-01-01 00:00:00
abstract：:N-acetyltransferase 1 (NAT1), a polymorphic Phase II enzyme, plays an essential role in metabolizing heterocyclic and aromatic amines, which are implicated in urinary bladder cancer (BCa). This systematic review investigates a possible association between the different NAT1 genetic polymorphisms and BCa risk. Medline,...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,meta分析,评审
doi：10.1080/03602532.2017.1415928
更新日期：2018-05-01 00:00:00
abstract：:Monkeys, especially macaques, including cynomolgus (Macaca fascicularis) and rhesus monkeys (Macaca mulatta), are frequently used in drug metabolism studies due to their evolutionary closeness to humans. Recently, numerous cytochrome P450 (P450 or CYP) cDNAs have been identified and characterized in cynomolgus and rhe...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2010.549492
更新日期：2011-08-01 00:00:00
abstract：:Much is known about the distal DNA damage repair response. In particular, many of the enzymes and auxiliary proteins that participate in DNA repair have been characterized. In addition, knowledge of signaling pathways activated in response to DNA damage is increasing. In contrast, comparatively less is known of DNA da...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530600959649
更新日期：2006-01-01 00:00:00
abstract：:The multistep, clonal evolution model of cancer predicts fundamental mechanisms by which chemicals may influence the cancer process. These are illustrated by studies of the mechanisms of induction of carcinogenesis by estrogens and the inhibition of carcinogenesis by caloric restriction. ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-100100567
更新日期：2000-05-01 00:00:00
abstract：:Synthetic cannabinoids (SC), originally developed as research tools, are now highly abused novel psychoactive substances. We present a comprehensive systematic review covering in vivo and in vitro animal and human pharmacokinetics and analytical methods for identifying SC and their metabolites in biological matrices. ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2015.1029635
更新日期：2015-05-01 00:00:00
abstract：:Numerous experimental and epidemiological studies have demonstrated that polycyclic aromatic hydrocarbons (PAHs), which are major constituents of cigarette tobacco tar, are strongly involved in the pathogenesis of the cardiovascular diseases (CVDs). Knowing that PAH-induced toxicities are mediated by the activation of...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530600632063
更新日期：2006-01-01 00:00:00
abstract：:Drug transporters and drug metabolism enzymes govern drug absorption, distribution, metabolism and elimination. Many literature works presenting important aspects related to stereochemistry of drug metabolism are available. However, there is very little literature on stereoselectivity of chiral drug transport and enan...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2014.887094
更新日期：2014-08-01 00:00:00
abstract：:Cytochrome P450 (CYP) 2D6 is one of the most important enzymes involved in the metabolism of drugs. Multiple, clinically relevant, genetic variants of this gene have been identified and, among them, a gene deletion as well as multiplications of the gene. These large structural mutations in CYP2D6 occur at a relatively...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530600952206
更新日期：2007-01-01 00:00:00
